Global malaria control is threatened by antimalarial drug resistance. New antimalarial therapies and a better understanding of the mechanisms of drug resistance are urgently needed. The overall goals of this project are to evaluate the efficacy of alternative therapies for uncomplicated falciparum malaria in a setting of high chloroquine resistance and to study the epidemiology of malaria using molecular techniques. The specific aims of this project are: 1) to compare the efficacy of combinations of antimalarial drugs with a standard monotherapy regimen for the treatment of uncomplicated falciparum malaria in Kampala, Uganda; 2) to distinguish recrudescence from new infections after antimalarial treatment by molecularly "fingerprinting" strains of P. falciparum; and 3) to characterize the molecular basis of resistance to common antimalarial therapies. Ultimately, this investigation of falciparum malaria in Uganda will provide relevant information applicable to the formulation of drug treatment and malaria control policies and will contribute to our understanding of antimalarial drug resistance. The candidate is an infectious disease clinician with a career interest in international health. The career development plan detailed in this proposal will integrate her prior experiences with new expertise in the epidemiology of drug resistant malaria and provide a solid foundation for research and a career in academic medicine. The intellectual environment at the University of California, San Francisco and the collaboration between UCSF, Makerere University in Kampala, Uganda and the University of California, Berkeley, School of Public Health afford the candidate an opportunity to pursue her career development plan.